Submissions for variant NM_000455.5(STK11):c.597+14del

gnomAD frequency: 0.00067  dbSNP: rs536282050

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160973	SCV000211682	benign	Hereditary cancer-predisposing syndrome	2014-02-21	criteria provided, single submitter	clinical testing	The variant is found in BR-OV-HEREDIC,COLO-HEREDIC panel(s).
Illumina Laboratory Services, Illumina	RCV000352916	SCV000410739	likely benign	Peutz-Jeghers syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Counsyl	RCV000352916	SCV000488965	likely benign	Peutz-Jeghers syndrome	2016-07-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160973	SCV000686666	likely benign	Hereditary cancer-predisposing syndrome	2015-04-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679321	SCV000806083	likely benign	not provided	2017-10-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000679321	SCV002048364	likely benign	not provided	2021-07-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000352916	SCV002057419	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000352916	SCV002366531	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000160973	SCV002658361	likely benign	Hereditary cancer-predisposing syndrome	2014-11-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465540	SCV002761024	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149982	SCV003838159	likely benign	Breast and/or ovarian cancer	2023-05-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000679321	SCV004701684	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	STK11: BS1
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356292	SCV001551420	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 c.597+14delA variant was not identified in the literature nor was it identified in the Cosmic, MutDB, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs536282050) as “With Likely benign allele,” ClinVar (as benign by GeneDx and likely benign by Illumina, Counsyl, and Color Genomics), Clinvitae (2x as in ClinVar), and LOVD 3.0 (2x as likely benign) databases. The variant was identified in control databases in 1 of 30810 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 8678 chromosomes (freq: 0.000115), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (Non-Finnish), Latino, Other, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified with a co-occurring pathogenic NBN variant (p.Lys233SerfsX5), increasing the likelihood that the c.597+14delA variant does not have clinical significance. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000679321	SCV001807663	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000679321	SCV001923292	likely benign	not provided		no assertion criteria provided	clinical testing